ACE Gene: Function, Mutations, and Associated Diseases | Biomedical Resource

The ACE gene encodes angiotensin-converting enzyme, a zinc metallopeptidase that cleaves angiotensin I to angiotensin II, a potent vasoconstrictor, and inactivates bradykinin, a vasodilator. This enzyme plays a central role in the renin-angiotensin system, regulating blood pressure, fluid and electrolyte balance, and vascular remodeling. ACE is expressed on the surface of endothelial and epithelial cells, and its soluble form circulates in plasma. Genetic variants in ACE, particularly an insertion/deletion (I/D) polymorphism, are associated with altered enzyme levels and susceptibility to cardiovascular, renal, and pulmonary diseases, including hypertension, diabetic nephropathy, and acute respiratory distress syndrome (ARDS).

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Renin-angiotensin system (RAS)

• Bradykinin degradation pathway

• Regulation of blood pressure by the renin-angiotensin system

• ACE inhibitor pathway (pharmacological)

The ACE protein is a type I transmembrane glycoprotein of 1306 amino acids, with a large extracellular domain containing two homologous zinc-binding motifs, each with catalytic activity. It is expressed as a membrane-bound ectoenzyme on endothelial and epithelial cells, and a soluble form is generated by proteolytic cleavage. ACE cleaves the C-terminal dipeptide from angiotensin I to produce angiotensin II, and inactivates bradykinin by sequential cleavage. The enzyme is a key target for antihypertensive drugs (ACE inhibitors). Its activity is modulated by genetic polymorphisms, particularly the I/D variant, which affects plasma and tissue ACE levels. The protein structure includes a signal peptide, a short cytoplasmic tail, and a transmembrane domain. Post-translational modifications include glycosylation, which is essential for proper folding and activity.